Index to Anti-Aging Medicine
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A: Aa - Am
A4M [Links] - American Academy of Anti-Aging Medicine (Site), sources [57].
AC-11 [Links; Papers/Cat's Claw extract for DNA repair, Patents, Books, LifeExtension; Video/Cat's Claw Extract, AC-11 (Optigenex Site)]. AC-11 is a DNA repair enhancer [Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension, (10)] formerly named C-Med-100, Dr. Ronald Pero's Cat's Claw Extract [Links, Images, Video, Papers, Patents, Books]. AC-11 is available as C-MED-100 through Prothera. [Patents/Cats Claw Extract]. Cat's Claw is also termed Uncaria tomentosa [Links, Images, Video, Papers, Patents, Books]. See Sheng Y, Li L, Holmgren K, Pero RW (2001), DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study, Phytomedicine, 2001 Jul;8(4):275-82.
Acai berry [Wikipedia/Acai Palm, Links, Images, Video, Papers, Patents, Books, Ray, LifeExtension, Amazon] The acai berry, a food first consumed by the Amazonian indians, has powerful antioxidant properties. Acai berries are the fruit at the top of the ORAC scale. The acai berry is purple and small and comes from a palm tree known by the Brazilians as "the tree of life." The medicinal substances of the acai berry include polyphenols [High and Low Polyphenol Links, Video/polyphenols, Index, Wikipedia, LifeExtension], flavonoids [Video/flavonoids, Wikipedia, LifeExtension], primarily anthocyanins [Video/anthocyanins, Index, Wikipedia, LifeExtension] and proanthocyanidins [Wikipedia, LifeExtension]. Freeze-dried acai extract is most effective against superoxide, hydroxyl, and peroxyl radicals. (LEF, June 2010). In addition, Acai inhibits COX-1 and COX-2 enzymes, making it effective against pain and inflammation. Acai is effective as a vasodilator. (Michael Downey, 2013). Acai also inhibits the spread of colon cancer and leukemia. See Roni Enten, The Secret Behind Acai, Life Extension Magazine, June 2010. (See the ORAC antioxidant value of foods.) Note that acai berry is effective against the most destructive reactive oxygen species (ROS), including peroxynitrites that cause lipid peroxidation, like gamma tocopherol in peanuts, and also against the hydroxyl radical, and the destructive superoxide and peroxyl radicals. See Ames BN, Shigenaga MK, Hagen TM (1993), Oxidants, antioxidants, and the degenerative disease of aging, Proceedings of the National Academy of Sciences USA, 1993 Sept 1;90(17):7015-22. Poon HF, Calabrese V, Scapagnini G, Butterfield DA (2004), Free radicals and brain aging, Clinical Geriatric Medicine 2004 May;20(2):329-59. Mertens-Talcott SU, Rios J, Jilma-Stohlawetz P, et al. (2008), Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich acai juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers, Journal of Agricultural and Food Chemistry 2008; 56:7796-802. Schauss AG, Wu X, Prior RL, Ou B, Huang D, Owens J, Agarwal A, Jensen GS, Hart AN, Shanbrom E (2006), Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe olecaceae mart. (acai). Journal of Agricultural and Food Chemistry 2006 Nov 1; 54(22):8604-10.
Acarbose (Precose) [Wikipedia, IAAS/Acarbose (Precose), Links, Images, Video, Papers, Patents, Books, LifeExtension]. Acarbose simulates caloric restriction (CR), used in diabetes treatment, has some side-effects, including excess gas. [91].
Acetyl L-Carnitine [IAAS/Acetyl L-Carnitine, info, QC, Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon, LibCong, Ben Best/Acetyl L-Carnitine, Antiaging-Systems/Carnitine; sources, toxicity, side effects, dosage; Carnitine], (4), (5), [58]. Acetyl L-carnitine is used to treat oxidative stress, to improve mitochondrial function, and to improve the expression of nerve growth factor. Acetyl L-Carnitine is useful in treating mitochondrial aging when given with alpha lipoic acid (Video). Then it makes old rats behave like young ones [Terraternal/Alpha Lipoic Acid/Articles]. See also Acetyl L-Carnitine in bodybuilding, and as a nootropic [Index, Links], in treating mitochondrial aging. Acetyl L-Carnitine with alpha lipoic acid [Index, Links, Video] rejuvenates aging mitochondria [Links, Papers, Books; LifeExtension/mitochondrial rejuvenation, Links, Videos], and appears to solve most problems posed by mitochondrial factors in aging [Links, Papers, Patents, Books, Amazon, Terraternal/Acetyl L-Carnitine]. Also consider [Ray/Acetyl L-Carnitine, Life Extension Abstracts, ImmuneSupport/Alpha Lipoic Acid; Links/Acetyl L-Carnitine with Alpha Lipoic Acid, Images]. Note that pre-treatment of monkeys with acetyl-L-carnitine prevents artificially induced Parkinson's Disease. Acetyl L-carnitine was developed by scientists as a more bioavailable form of L-carnitine and must be taken as a supplement. Acetyl L-Carnitine has been reported as elevating Nerve Growth Factor (NGF) by as much as 100 times. Nerve Growth Factor promotes Id-1 helix-loop-helix transcription factor protein, which can activate telomerase expression and inhibit transcription of the tumor suppressor protein p16INK4a (Zheng et al. 2004, Ohani et al. 2001), which can accumulate until it induces cellular senescence and inhibits neural forebrain progenitors, reducing neurogenesis. Note that Acetyl L-carnitine is present in the cerebral and peripheral nervous system, where its presence is required for normal nerve conduction. See the US Patent by Claudio Cavazza (2002), Antioxidant Composition Comprising Acetyl L-Carnitine and Alpha-Lipoic Acid. The carnitines stabilize cellular phospholipid membranes, assist in the production of energy by mitochondrial beta-oxidation of fatty acids, and protect cerebral tissue against peroxidation. Reduced levels of the carnitines have been detecting during aging, accompanied by reduced cardiolipin concentrations in mitochondrial membranes. Acetyl L-carnitine, when applied to aging specimens,restores mitochondrial beta-oxidation of fatty acids and cardiolipin concentrations in mitochondrial membranes that play an important role in this process. Acetyl L-carnitine also restores levels of IGF-1 in aging neural tissue. The growth-promoting effect of IGF-1 on brain cells is potentiated by acetyl L-carnitine plus alpha lipoic acid. The release of nitric oxide in endothelial tissues is promoted by acetylcholine, which is elevated by acetyl L-carnitine. See Peng Zhou, Zhuo Chen, Ning Zhao, Dan Liu, Zi-Yuan Guo, Lu Tan, Juan Hu, Qun Wang, Jian-Zhi Wang, and Ling-Qiang Zhu (2011), Acetyl-L-Carnitine Attenuates Homocysteine-Induced Alzheimer-Like Histopathological and Behavioral Abnormalities, Rejuvenation Research December 2011, 14(6): 669-679.
Acetyl L-Carnitine Arginate [Links, Images, Video, Papers, Patents, LifeExtension], (See Acetyl L-Carnitine with one molecule of L-Arginine) Life Extension formula stimulates neurite growth as much as nerve growth factor (NGF) [Links/Acetyl L-Carnitine]. (5), [58]. Note that NGF levels were significantly higher for experimental subjects in love, and that levels stayed high for a year after falling in love. Carnosic acid (from Rosemary or aroma therapy's Essential Oil of Rosemary) also elevates Nerve Growth Factor. (Wikipedia/Nerve growth factor, Video). For brain regeneration [Books, Video] see also the index entries for Brain Deterioration, Arginine, Vinpocetine, Gotu Kola, Ashwagandha, and DHA and try Links/neuroregeneration, Links/drugs promoting neurite growth.
Activated Macrophages [Links, Images, Video, Papers, Patents, Books, LEF]. Activated macrophages produce ROS, Reactive Oxygen Species. [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Antioxidants may be taken to counteract ROS, or endogenous antioxidants may be boosted with drugs like Ashwagandha and Huperzine A. Use of antiglycating drugs (Index/Antiglycating Drugs, including carnosine and Vitamin C) and avoiding glycation [Index] from Maillard reaction products also reduces ROS.
Adenovirus transfection [Wikipedia/Adenovirus, Video/Adenovirus, Wikipedia/Gene therapy, Wiki/Viral vector; QbioGene/Adenovirus for gene therapy applications; Links/Adenoviral Transfections, Images, Video, Papers, Patents, Books, Amazon, LibCong; Invitrogen/adenoviral transfections, Amaxa Biosystems, Amazon/adenoviral transfections; Books/viral transfection techniques for gene therapy, Books/gene therapy with DNA plasmids, Books/gene therapy for anti-aging; Books/Gene Therapy, Amazon, Video]. Gene therapy via adenovirus transfection is always safer than gene therapy with lentiviruses, because the adenovirus always integrates into the same position in the genome [Images]. The adenovirus genome is composed of between 26 and 45 Kbp of nonsegmented, linear, double stranded DNA. "This allows the virus to theoretically carry 22 to 40 genes." - Wikipedia/Adenovirus. hTERT has an estimated size of about 40kb.
Adeno-associated virus (AAV) [Wikipedia, Links/Adeno-associated virus transfection, Images, Video, Papers, Patents, Books, Video/transduction]. Adeno-associated virus brings about a very mild immune system response, integrates into the genomes of both dividing and non-dividing cells, and is now a promising candidate for gene therapy applications. The adeno-associated virus AAV always integrates into the same site AAVS1 [Wikigenes] on chromosome 19 [Images]. "The cloning capacity of the vector is relatively limited and most therapeutic genes require the complete replacement of the virus's 4.8 kilobase genome, which is composed of single-stranded DNA. Large genes are, therefore, not suitable for use in a standard AAV vector." - Wikipedia/Adeno-associated_virus. Note that the < 900 bp green fluorescent protein genetic code fits easily into an AAV virus [AAV virus]. It may be useful to program AAV viruses with synthetic genes incorporating short peptide bioregulators like epithalon peptide (Ala-Glu-Asp-Gly), Livagen (Lys-Glu-Asp-Ala) or Vilon (Lys-Glu), together with a suitable promoter such as the hTERT promoter. Twelve different serotypes [Wikipedia/Serotype, Links] of AAV (AAV1-AAV11) exist, differing with the respect to the cell surface receptors they are bound to. Note that some recent work (Patent EP 2402038 A1) describes the AAV vectors as non-integrative, not having permanent effect on the genome, contradicting part of the above description, and only having effect for a limited number of years.
(1) AAV1 is efficient in gene delivery to vascular endothelial cells and murine skeletal cells.
(2) AAV2 uses three receptors (the heparan sulfate proteoglican (HSPG) cell receptor, the aVbeta5 integrin cell receptor, and the fibroblast growth factor receptor 1). AAV2 may be used to transfect skeletal muscles, neurons, vascular smooth muscle cells and hepatocytes, and apparently kills cancer cells without harming healthy ones. See liver cancer and brain cancer.
(3) AAV3 [Images]. Adeno-associated virus (AAV)-3-based vectors transduce haematopoietic cells not susceptible to transduction with AAV-2-based vectors.
(4) AAV4 transduction can be inhibited by soluble sialic acids (of different form for each of these serotypes), like AAV5.
(5) AAV5, like AAV1, is very efficient in gene delivery to vascular endothelial cells and murine skeletal cells. AAV5 transduction can be inhibited by soluble sialic acids, and AAV5 was shown to enter cells via the platelet-derived growth factor receptor [Images, Papers, Patents, Books].
(6) AAV6 (a hybrid of AAV1 and AAV2) is useful in infecting airway epithelial cells. AAV6 also shows lower immunogenicity than AAV2.
(7) AAV7 presents very high transduction rate of murine skeletal muscle cells (similarly to AAV1 and AAV5).
(8) AAV8 is superb in transducing hepatocytes.
(9) AAV9 may be an optimal vehicle for body-wide gene delivery.
hTERT may be reliably transfected using the AAV9 viral capsid (Patent, Notes).
Non-integrative viruses made from AAV virus components including hTERT featuring a CMV promoter may be used. Modified transfection therapy to avoid rejection may be repeated every 5 years using different AAV serotype components. Perhaps a more compact hTERT cDNA without introns may be used in single-stranded form for insertion into the AAV serotypes as an integrative virus if the single-stranded hTERT DNA length is less than 4.8 Kb. Adding the 16 exon lengths of hTERT together, I find 3396 nt length, 3.396 Kb. The CMV promoter length is 508 nt, so that hTERT cDNA with CMV promoter should come to 3904 nt or 3.904 Kb. Using the canonical 181-bp hTERT core promoter 19 bp upstream of the first nucleotide in the cDNA sequence instead would yield hTERT cDNA + core promoter = 3396+181+19 nt = 3596 nt = 3.596 Kb.
(10) AAV10. AAV10 and AAV11 Serologically Cross-React with AAV8 and AAV4.
(11) AAV11. AAV10 and AAV11 Serologically Cross-React with AAV8 and AAV4.
(12) AAV12. Sialic Acid- and Heparan Sulfate Proteoglycan-Independent Transduction.
The hTERT gene or other genes such as C-myc for hTERT activation to keep telomeres long may be transfected using adenovirus vectors, and alternative gene therapy techniques exist. I note that C-myc [Index/C-myc] can become unregulated, however, when it is translocated due to the action of some viral pathogens, making it an oncogene [Links/Oncogenes] associated with cancers such as Burkitt's Lymphoma under certain conditions. See also [Index/Transfection, Index/Gene Therapy, Links/Gene Therapy Safety Issues, Links/Safety Issues in Adenovirus Transfection for Gene Therapy Applications]. So far, the adenovirus looks comfortable for in vitro cell cultures, and I gather healthy experimenters survive In Situ adenovirus transfection, although one or two patients have not recovered from gene therapy implemented with adenovirus transfection.
Adipocyes (Encyclopedia).
Adrenal Fatique [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Also see Adrenal Burnout, Adrenal Failure. The adrenal gland is located on top of the kidney. The adrenal glands produce dihydroepiandrosterone (DHEA), a precursor of testosterone, and other adrenal hormones.
Adult Stem Cells [Index/Stem Cell Technology, Wikipedia, LifeExtension/Adult stem cells, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; (8)]. Adult stem cells can be induced to behave like embryonic stem cells in mice. See also Life extension with adult stem cells and adult stem cells in anti-aging medicine.
Advanced Cell Technology [Links/Advanced Cell Technology, Video, Books, Patents/biological cell technology]. Advanced Cell Technology Company Site, [9].
Advances in Cell Aging and Gerontology - Journals/Advances in Cell Aging and Gerontology on-line. See Journals.
Adrafinil [Wikipedia, Links, Images, Video, Papers, Patents, Books, IAAS, LifeExtension]. Adrafinil / Olmifon Enhances Mental Clarity and Alertness. Eurodrug. See supplements for enhancing mental clarity and alertness, anti-aging European drugs, and European drugs for enhancing mental clarity and alertness.
Ageing [Ageing, Universe Review, Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LibCong]. See also Human Aging in India, with process factors. See Journals. See Jan Vig and Judith Campisi (2008), Puzzles, Promises, and a Cure for Aging, (full text), Nature, 454, 1065-1071 (28 August 2008), with Figure 1: Potentially conserved pro-ageing pathways, their interconnections and possible targets for intervention. See pro-aging pathways [Links, Images, Video, Papers, Patents, Books] and targets for intervention in pro-aging pathways [Links, Images, Video, Papers, Patents, Books]. According to Aubrey de Grey, aging accounts for 90% of deaths in the industrial world and for two-thirds of deaths in the rest of the world. - Aubrey de Grey, (2011), Why Aren't More Wealthy People Funding Aging Research?, Life Extension Magazine, September 2011. For a stimulating grab-bag of cures to aging problems, see the US Patent by Shyam K. Gupta and Linda Walker (2011), Prevention of Cellular Senescence in Mammals by Natural Peptide Complexes. Also see Digital Aging Atlas.
Age and Ageing - Journals/Age and Ageing. See Journals, Digital Aging Atlas.
Aging Research Reviews [Links] Aging Research Reviews (Journal Site). See Journals.
AGE inhibitors [QC/AGE inhibitors, Links, Images, Video, Papers, Patents, Books, LibCong, article, LifeExtension; Index/AGEs], (3). See
AGE inhibitors:
__pimagedine [Wikipedia, Links, Images, Papers, Patents, Books, LEF],
_____an AGE inhibitor from Alteon, and a component of vitamin B6 [LifeExtension],
__pyridoxamine [article, Links, Images, Papers, Patents, Books, Wikipedia, IAAS, LEF].
__aminoguanidine (pimagedine) [Links, Images, Papers, Patents, LEF; Links/side effects],
__carnosine [Wikipedia, Links, Images, Video, Papers, Patents, Books, LEF],
__phenazinediamine [Links, Images, Papers, Patents, Books, LEF],
__OPB-9195 [Links, Images, Papers, Patents, Books, LEF],
__tenilsetam [Links, Images, Papers, Patents, Books, LEF],
__rhodiola rosea [Links, Images, Video, Papers, Patents, Books, LEF], and the
AGEs protection tips - more AGE inhibitors:
__"Taurine protects against the formation of AGEs...
__Rutin, a citrus flavonoid, strongly protects against glycation effects...
__Polyamines produced from L-arginine, protect against AGEs...
__Creatine protects against AGEs."

AGE-breakers (glycation crosslink breakers):
__phenacylthiazolium [Links, Images, Papers, Patents, LEF] and
__phenacyldimethylthiazolium bromide [Links, Images, Papers, Patents, LEF].
- Jerry Brainum, Coming of AGEs, Iron Man Magazine, Summer 2010.
AGE-formation accelerators (after Brainum)
__Methamphetamines accelerate the formation of AGEs.
__High blood sugar enhances the formation of AGEs and their mitochondrial accumulation.
__Kidney function loss contributes to the accumulation of AGEs.
__Cooking food (Maillard reaction) enhances the formation of AGEs.
Advanced Glycation End products (AGEs) [Wikipedia, Links/Advanced Glycation End products (AGEs), Images, Video, Papers, Patents, Books, LibCong, Amazon, article, LifeExtension; Index/AGE Inhibitors; Mortality/Glycation].

Age in Years
Fluorescence of AGEs due to glycation in human tissue VS. Age in years.
After Annette T. Lee and Anthony Cerami (2006), The Role of Glycation in Aging [PDF], NY Acad Sci, 17 Dec 2006. Glycation (5) from reducing sugars such as glucose damages proteins and DNA, leading to higher ROS levels, inflammation, activation of NF-kB, and sometimes Alzheimer's Disease. Antiglycation Agents include benfotiamine (onions), carnosine, vitamin B1, vitamin C, and green tea. Damage from glycation and AGEs (5) can often be prevented or reversed with acetyl L-carnitine, alpha lipoic acid, and CoQ10. "The formation of Advanced Glycation End-products (AGEs) by oxidation of Amadori products is irreversible. AGEs in tissues increase the rate of free radical production to 50-times the rate of free-radical production by unglycated proteins.", (5). Note that "browning of food by boiling or frying can increase AGE content 3-5 fold", and that "high AGE content in food elevates inflammatory markers". - Caleb E. Finch, p.129. AGEs are ligands for RAGE receptors [Links, Images, Papers, Patents] producing inflammatory cytokines. AGEs include
__glucosepane [Wikipedia, Links, Images, Books, Papers, Patents, LifeExtension],
__K2P (eye lens) [Links, Images, Papers, Patents, Books], and
__pentosidine [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension], with glucosepane typically 50% higher in skin collagen than pentosidine. - Caleb E. Finch, p.39. "The two most commonly measured AGEs, N-(carboxymethyl)lysine [Wikipedia/N(6)-Carboxymethyllysine] and pentosidine, are glycoxidation products [Books], formed from glucose by sequential glycation and autoxidation reactions." [Price, Rhett, Thorpe, and Baynes, 2001]. See also Index/AGE inhibitors. Note that diabetics with elevated blood glucose may seem to age 5x as fast as ordinary people, and markers of glycation increase five-fold from infancy to old age (Brainum, op.cit.)
Age Progression and Regression (Encyclopedia)
Aging - Definition [Ben Best/Aging - Definition, Links/mechanisms of cellular senescence, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension].
Aging and Cancer [Jerry Shay/Aging and Cancer: Are Telomeres and Telomerase the Connection?, Links/Cancer & Aging, Images, Video, Papers, Patents, Books, LibCong, LifeExtension]. See Index/Cancer and Index/Carcinogens, and the index entries below on anti-cancer diet and anticarcinogens.
Aging - Associated Phamaceutical Industry [Longevity Supplement Vendors, Piribo/Aging - Associated Phamaceutical Industry, Pharmaceutical Vendors, Links/Antiaging Pharmaceuticals, Images, Video, Papers, Patents, Books, LibCong, LifeExtension Foundation; Wikipedia/Biopharmaceuticals; Links/drug discovery, Books; Links/pharmaceutical engineering, Index/Pharmaceutical Engineering].
Aging, Life Span, and Senescence - PNAS/article/Aging, Life Span, and Senescence, [53].
Aging - Symptoms [Ben Best/Aging - Symptoms, Links, Images, Video, Papers, Patents, Books, LifeExtension].
Aging and Sex - Ben Best/Aging and Sex, Aging and Sex Organs, Ben Best/Sex Hormone Replacement in Older Adults. [Links/Sex hormone replacement, Images, Video, Papers, Patents, Books, LifeExtension]. The sex hormones estrogen [Links, Images, Video, Papers, Patents, Books, LifeExtension, Images/estrogen supplements, Telomerase Activators/Estrogen] and progesterone [Links, Images, Video, Papers, Patents, Books, LifeExtension, Images/Progesterone supplements, Telomerase Activators/Progesterone] are associated with activation sites on the hTERT promoter (although they act through receptors on the cell membrane surface), and thus activate telomerase production via intermediate transcription factors. In this way, sex may be associated with long life, and women do seem to live longer than men on the average, according to our mortality charts. Male androgens are also associated with telomerase activation, perhaps after their conversion to estrogens by aromatase, as they are more indirectly associated with activation sites on the hTERT promoter. See Telomerase Activators (7). According to Gomez-Garcia, et al., all human growth hormones including HGH, IGF-1, FGF, and Hepatocyte Growth Factor, activate telomerase, so that sex hormones are by no means the only hormonal route to telomerase activation. The Gomez-Garcia rule applies to most human growth factors [Index].
Aging of Non-Sexual Organs [Ben Best/Aging of Non-Sexual Organs, Links, Images, Video, Papers, Patents, Books, LifeExtension].
Aging - Ben Best/Species Specific Aging and Evolution [Links/Evolution & Aging, Images, Video, Papers, Patents, Books, The Evolution of Aging (on-line) by Theodore C. Goldsmith, LifeExtension, Amazon].
Aging - The Molecular Concepts [Innovita/Aging - The Molecular Concepts, Innovita Research Corporation, Links/Aging at the Molecular Level, Images, Video, Papers, Patents, Books; Books/The Molecular Basis of Aging, Amazon/Aging at the Molecular Level, LibCong/Aging at the Molecular Level, Ben Best/Mechanisms of Aging]. See also (7) Telomere Theory and Hayflick, His Limit, and Cellular Aging by Shay & Wright, and the Nobel Prize Winner's essay Telomeres and Telomerase: the path from maize, Tetrahymena, and yeast to human cancer and aging by Elizabeth H. Blackburn, Carol W. Grieder, and Jack W. Szostak.
Aging Brain: What Causes It [Brain, Brain Cancer, Brain Deterioration, Cognitive Decline, Dementias, Neurobiology of Aging, Leukoaraiosis, Hypoperfusion, Neurodegenerative Disorders; Links/Aging Brain, Images, Video, Papers, Patents, Books, LibCong/The Aging Brain, LifeExtension; Journal of Longevity/Aging Brain: What Causes It; Wikipedia/Neurodegenerative Disease, Links/Neurodegenerative Disease, Images, Video, Papers, Patents, Books, LifeExtension, Amazon], (5). See Prolla TA (2002), DNA Microarray Analysis of the Aging Brain [Links, Images, Video, Papers, Patents, Books], Chem Senses, 27:299-306.
Aging and cellular garbage accumulation [Links, Images, Video, Papers, Patents, Books, Ingentaconnect/Aging and cellular garbage accumulation, LifeExtension, LifeExtension/cellular garbage], [4s, (4), (12), (13)]. Intracellular garbage includes Lipofuscin, Ceroid Deposits, Amyloid-Beta, and Lewis Bodies. Potassium accumulates in nerve cells according to the Membrane Hypothesis of Aging (4), (13). Accumulating p16INK4a [Index] makes recovery of cells from cellular senescence difficult. Extracellular systemic garbage is also very impacting. See Atherosclerotic Plaque, Testosterone for reverse cholesterol tranport, Vitamin D and Vitamin K2 for decalcification of atherosclerotic plaque and reversing systemic calcification, Amyloid Beta, Amyloid Beta Inhibitors for eliminating amyloid plaque, and Metal Ions. Curcumin chelates aluminum, which produces to neurofibrillary tangles associated with Alzheimer's Disease. Also see Smoking and Main Essay/Smoking.
Aging Research Center (ARC) [Links/aging research centers, Images, Video, Papers, Books] [14].
Aging in Yeast, [Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension], [3s].
AIDS Virus See HIV.
AKT Kinases [Telomerase activators/AKT, Wikipedia/Akt, Wikipedia/Akt1, Links/Akt kinase, Images, Video, Papers, Patents, Books; Links/Nutraceuticals promoting Akt kinase, Images, Video, Papers, Patents, Books; Wikipedia/Akt protein kinase, Links, Images, Video, Papers, Patents, Books; Biocarta Pathways/Telomerase Activation, PI3K/AKT Pathway; Index/Longevity Genes]. There are 3 genes associated with the AKT kinases, AKT1, AKT2, and AKT3 that produce the 3 different AKT isoforms. Kinases phosphorylate hTERT protein in the cytoplasm for import into the nucleus. As far as I am aware, they do not interact with the hTERT promoter. (Check.) See the PI3K/AKT hTERT activation pathway and hTERT activation via AKT1. See also hTERT activation via the MAP kinase pathway. Note that resveratrol activates telomerase activity via AKT1, although it also activates SIRT1, which deacetylates DNA with HDAC effect, compacting chromatin and generally repressing transcription with gene silencing. Ordinarily, this represses transcription of hTERT. Conversely, HDAC inhibitors like Tricostatin A often promote hTERT activity by expanding chromatin via acetylation of histones, enabling hTERT mRNA transcription. See Kang SS, Kwon T, Kwon DY and Do SI, 1999, Akt protein kinase enhances human telomerase activity through phosphorylation of telomerase reverse transcriptase subunit, Journal of Biological Chemistry, 274, 13085-13090. Furthermore, AKT1 activity protects telomeres. See Xin Han, Dan Liu, Yi Zhang, Yujing Li, Weisi Lu, Junjie Chen and Zhou Songyang (2013), Akt regulates TPP1 homodimerization and telomere protection, Aging Cell (2013) 12, pp1091–1099. Akt1 kinase seems to be the Akt protein kinase acting in association with growth factors such as IGF-1. See the IGF-1/PI3K/AKT pathway for activation of hTERT. See Links/Akt protein kinase enhances human telomerase activity. Note that the PI3K family is a large family of lipid kinases and serine/threonine kinases. See also Bryan T. Hennessy, Debra L. Smith, Prahlad T. Ram, Yiling Lu, and Gordon B. Mills (2005), Exploiting the PI3K/AKT Pathway for Cancer Drug Discovery, NATURE Reviews Drug Discovery, Dec 2005, Vol.IV: "Numerous components of the phosphatidylinositol-3'-kinase are targeted by amplification, mutation, and translocation more frequently than any other pathway in cancer patients." Note that AKT2 is genomically amplified in pancreatic, breast, and ovarian tumors. AKT3 is overexpressed in hormone-insensitive breast cancers and prostate cancers. Finally, AKT can inactivate p53 through mdm2, contributing to centrosome hyperamplification and chromosome instability in cancer. Note that the PI3/AKT/mTOR pathway exists for activating mTOR (mammalian Target Of Rapamycin) with AKT. - Wikipedia/PI3K/AKT/mTOR_pathway. Note that folic acid (vitamin B9) supplements stimulate the PI3K/AKT signaling cascade. See phosphorylates hTERT.
AKT and phosphorylation
By now we realize that phosphorylation of the hTERT catalytic component of telomerase can "activate" existing hTERT molecules (so that they can be transported from the cytoplasm into the nucleus) without supplying a transcription factor that increases the number of hTERT mRNA transcripts. Usually "telomerase activators" increase the number of hTERT mRNA transcripts. It will be useful to keep this difference in mind while analyzing "telomerase activators". The AKT protein kinase phosphorylates hTERT in the cytoplasm to enable its transport into the nucleus. AKT is not a transcription factor, but a kinase with a mission to phosphorylate a protein.
From a bodybuilding point of view (and to avoid old age sarcopenia), the IGF-1/PI3K/AKT pathway is anabolic and induces muscular hypertrophy, also preventing the induction of the atrophy mediators, muscle-specific ubiquitin ligases including MAFbx and MURF1. "AKT is not only capable of activating prosynthetic pathways,.... but is able to suppress catabolic pathways, preventing glucocorticoid (cortisol) and denervation-induced muscle atrophy."
PI3-Kinase/Akt Pathway and FOXO
"Once activated, Akt phosphorylates a number of target proteins, including proteins that are direct regulators of cell proliferation and survival, transcription factors, and other protein kinases. The critical transcription factors targeted by Akt include members of the head or FOXO family. Phosphorylation of FOXO by Akt creates a binding site for cytosolic chaparone proteins (14-3-3 proteins) that sequester FOXO in an inactive form in the cytoplasm. In the absence of growth factor signaling and Akt activity, FOXO is released from 14-3-3 and translocates to the nucleus, stimulating transcription of genes that inhibit cell proliferation and induce cell death." - Geoffrey M. Cooper and Robert E. Hausman, The Cell: A Molecular Approach, 4th edition (2007), p. 624. See Exercise and AKT phosphorylation. The the IGF-1/PI3K/AKT pathway stimulated by exercise is not only anabolic, but prevents cell death due to FOXO. Phosphorylation of FOXO factors by Akt triggers rapid relocalization of FOXO transcription factors from the cellular nucleus to the cytoplasm, inhibiting the transcription of caveolin-1. Overexpression of caveolin-1 (gene CAV1) modifies the cellular membrane of senescent cells, preventing telomerase-activating growth factors such as EGF and PDGF from repairing telomeres and restarting the cell cycle to recover from cellular senescence. Inhibiting the transcription of caveolin-1 (with, say, cyclic AMP from exercise, or with folic acid) can cause cells to recover from the senescent phenotype and restore cellular sensitivity to telomerase-activating human growth factors enhanced by exercise, restarting the cell cycle and lengthening cellular telomeres. See therapy for recovering from cellular senescence, and cAMP, Growth Factors, and Activators for Senescent Cell Recovery.
Alagebrium (4,5-dimethyl-3-(2-oxo-2-phenylethyl)-thiazolium chloride) [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension; Index/AGE Inhibitors; Index/AGEs]. Alagebrium is Alteon's ALT-711, an Advanced Glycation End product cross-link breaker [Links, Images, Video, Papers, Patents, Books, LifeExtension] that softens tissue stiffened by AGEs, Advanced Glycation End products. A similar chemical is available. PTB (N-PhenacylThiazolium Bromide) [Links, Video, Links2, Papers, Patents, Books, LifeExtension] breaks cross-links a little less effectively than Alagebrium.
Alcohol [Alcoholism; Ben Best; Books/alcohol; Images/alcohol and longevity charts; Links/diseases and alcohol, Video, Images/alcohol charts, LibCong, Alcohol and Longevity, LifeExtension, Wikipedia/Long Term Effects of Alcohol]. Overeating plus smoking typically lowers longevity by 13 years. Throwing in immoderate drinking takes off substantially more, although moderate drinking may mildly improve heart disease statistics and longevity prospects. Overconsumption of alcohol can lead to liver cancer, colorectal cancer, gastrointestinal cancer, breast cancer, pancreatic cancer, gallstones, ceroid lipofuscin accumulation, and the sight of the breathalyzer coming. Furthermore, alcohol increases the likelihood of heart attack and of ischemic stroke. More than two drinks a day impedes bone repair and renewal, increasing fracture risk a href="#ALC2">[2].
In The French Paradox, drinking red wine extends longevity by providing SIRT1-activating resveratrol and quercetin, while alcohol improves their bioavailability. Resveratrol inhibits cancer from alcohol by destroying alcohol-damaged cells that become cancer cells (Adv Exp Med Biol 2015;815:333-48).
Silymarin, a powerful antioxidant from milk thistle, inhibits conversion of alcohol to acetylaldehyde and inhibits liver cancer cell proliferation and metastasis to improve liver health. Acetylaldehyde causes DNA damage in the form of DNA adducts. Silymarin promotes liver cell regeneration, and reduces inflammation. It also improves the survival time of liver cirrhosis victims.
N-Acetylcysteine (NAC) binds acetylaldehyde directly to prevent tissue damage from alcohol. Glutathione, selenium, benfotiamine, folic acid, SAMe, barley grass, grape seed extract, resveratrol, and chlorophyllin also help reduce the likelihood of cancer due to alcohol. Most deleterious effects of alcohol can be reversed with Picrorhiza kurroa (a south Asian member of the figwort family and a powerful antioxidant) [1]. Also see alcoholism for detoxification procedures and Alcoholics Anonymous.
References
[1] Michelle Flagg (2011),
Link Between Alcohol and Cancer Death, Life Extension Magazine, December 2011.
[2] Kanis, J. A., H. Johansson, O. Johnell, et al. (2005),
Alcohol intake as a risk factor for fracture, Osteoporos Int Jul;16(7):737–42.
ALEs - Advanced Lipid Oxidation End-products [Links/Advanced Lipid Oxidation End-products, Images, Video, Papers, Patents, Books; LifeExtension/ALEs, Amazon/Lipid Oxidation in Aging, Links/Advanced Lipid Oxidation End product inhibitors, Images, Video, Papers, Patents, Books, LifeExtension/Advanced Lipid Oxidation End product inhibitors].
Alkalinizing beverages [Links/Alkalinizing beverages, Links/Alkalinizing foods, Books, LifeExtension], acidosis in osteoporosis [Links, Video, Books], aging & pH of the blood [Books, LifeExtension], [72s], (1).
Allergic reactions to drugs [Intellihealth/Allergic reactions to drugs, Links, Images, Video, Papers, Books, LifeExtension; Links/Adverse Drug Reactions, Images, Papers, Books, LifeExtension, Amazon/Adverse Drug Reactions] (4).
Allicin [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension; Virology]. Allicin from crushed garlic [Index] is an anticancer small molecule telomerase inhibitor in cancer cells and a powerful antibiotic. Allicin metabolites diallyl disulfide and allyl mercaptan are HDAC inhibitors believed to improve the Hayflick Limit for dermal fibroblasts by expanding chromatin and increasing the transcription of hTERT mRNA in normal cells. Thus garlic is a telomerase activator for normal cells and improves the Hayflick Limit for dermal fibroblasts. It is believed to be effective against the HIV virus. Cinnamon, another powerful antiviral drug, is effective against HIV-1 and HIV-2. The most effective extracts against HIV-1 and HIV-2 were respectively Cinnamomum cassia (bark) and Cardiospermum helicacabum (shoot + fruit)." - Wikipedia/Cinnamon.
Alpha-Glycerylphosphorylcholine (Alpha-GPC) [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension, Ray Sahelian; LifeExtension/Cognitex; Images/molecule, Wiki/molecule; Links/the preparation of Alpha-GPC from lecithin, Images, Papers, Patents, Books]. Alpha-GPC comes from soy lecithin [molecule, Index], increases brain levels of acetylcholine, improves nerve cell growth and repair, used to support cognitive recovery from stroke or ischemic attack. Alpha-GPC is useful for treating old age cognitive decline, and is a primary component of Cognitex from the Life Extension Foundation. "Alpha-GPC has been proven to multiply the effects of the growth hormone releasing hormone (GHRH) and also increases the secretion of human growth hormone (HGH) from the pituitary gland in young and old patients," and thereby has applications in height increase in 17-25 year olds (bone lengthening) and in bodybuilding and antiaging. - Affordable Supplements. Nutrition53 claims better than x2 improvements in HGH levels from alpha-GPC lasting for about 60 minutes after exercise. Another source claimed alpha-GPC can boost HGH up to a factor of 44 in the presence of exercise, where exercise alone would produce a factor of 3 boost. Since HGH has been shown to activate telomerase [Notes], Alpha-GPC can be used with exercise to produce HGH for telomerase activation and rejuvenation. I note that alpha-glycerylphosphorylcholine is a component in some popularly available HGH secretagogues for rejuvenation applications. An example would be Secretagogue Gold from Aragon Products, which contains alpha-GPC. See obtaining alpha-glycerylphosphorylcholine from soy lecithin and extraction of soy lecithin from soy. See also soy, sources of soy, sources of soy lecithin, and sources of alpha-GPC.
Movie: Soylent Green, starring Charlton Heston.
Alpha Lipoic Acid [Wikipedia/Lipoic_Acid, Berkeley Wellness Guide/Alpha Lipoic Acid, QC, Links/Alpha Lipoic Acid, Images, Video, Papers, Patents, Books, Amazon LifeExtension, Images(supplements), Ray, Terraternal/Alpha Lipoic Acid Articles; Index/R-Lipoic Acid; sources, toxicity, side effects, dosage], [70], (1). Alpha lipoic acid is an antioxidant soluble in both oils and water that is anti-inflammatory, improves mitochondrial function, and helps to overcome insulin resistance. Alpha lipoic acid (ALA), discovered in 1951 as a Krebs cycle coenzyme, was understood to be a powerful antioxidant in the 1980s. It is soluble in watery and fatty regions of cells and is antioxidant in both its normal form and in its readily obtainable reduced form as dihydrolipoic acid (DHLA). Alpha lipoic acid (after internal conversion to DHLA) regenerates vitamin C and vitamin E and increases levels of glutathione and CoQ10. Alpha Lipoic Acid decreases the lipid peroxidation of nerve tissue, is good for sugar metabolism in preventing diabetes and in treating diabetic neuropathy, aids recovery from reperfusion injuries associated with strokes, and is useful in in bodybuilding to stimulate uptake of glucose by muscle cells, as a mitochondria protector, and in reversal of multiple sclerosis. ALA has two optical forms as R-lipoic acid and S-lipoic acid. After administration of a racemic mixture of R- and S-lipoic acid, R-lipoic acid is twice as prevelant in the blood as S-lipoic acid. See the commercially available redox couple of R-lipoic acid, R-Dihydro-Lipoic Acid. Note that R-lipoic acid reaches concentrations up 7 times higher than S-lipoic acid in the lens of the eye when a racemic mixture of alpha lipoic acid is orally administered. ALA prevents protein glycation and ultimately inhibits the formation of cataract-inducing sorbitol from glucose and galactose by inhibiting aldose reductase. Lipoic acid enhances insulin effects, lowering blood sugar levels, and inhibiting the formation of advanced glycation end products accelerating the onset of cardiovascular disease, brain degeneration, ocular disorders, and cancer. Furthermore, lipoic acid suppresses production of inflammatory cell-signaling molecules, while increasing production of molecules involved in vascular tone, such as endothelial nitric oxide synthase (eNOS). Alpha lipoic acid is capable of chelating arsenic, copper, cadmium, manganese, mercury, and zinc, and reduces toxicity due to oxidative stress in lead poisoning. It is useful for preventing radiation injury. Finally ALA or DHLA are used to inhibit viral replication of the HIV virus via inhibition of reverse transcriptase and NF-kB. The recommended therapeutic dose is 600-1800 mg daily.
Alpha Lipoic Acid with Acetyl L-Carnitine [LifeExtension, Links, Images, Video, Papers, Patents, Books]. Alpha lipoic acid with acetyl L-carnitine has been shown to restore mitochondria to a youthful state, and is thought to be the answer to the mitochondrial theory of aging. R Alpha Lipoic Acid chelates both copper and iron, helping it both oppose the spread of cancer via copper and helping it to protect hippocampal mitrochondria against copper and iron, opposing cognitive decline, dementia, and Alzheimers Disease. Alpha Lipoic Acid is soluble in both water and fats, making it relatively ideal as an antioxidant. Recently, sodium-R-lipoic acid [Links, Images, Papers, Patents, LEF] has been shown to be more bioavailable than lipoic acid (half active R-lipoic acid, half inactive S-lipoic acid) or pure R-lipoic acid, capable of achieving 10-30 times higher levels in the blood than R-lipoic acid, reaching peak plasma concentrations in just 10-20 minutes. See Life Extension's Super R-lipoic Acid, a brand of sodium-R-lipoic acid. "Alpha Lipoic Acid is able to regenerate vitamins E and C, CoQ10, glutathione and even its own self. It raises blood levels of glutathione, a powerful antioxidant. It is so effective at protecting against toxicity that it is being used in liver poisoning and in hepatitis C." - The Star, May 28, 2006." Note that alpha lipoic acid increases heat shock protein expression, including the expression of HSP90, which transports transcription factors into the cellular nucleus. See also Niku K. J. Oksala, Jani Lappalainen, David E. Laaksonen, Savita Khanna, Kai Kaarniranta, Chandan K. Sen, Mustafa Atalay, Alpha-Lipoic Acid Modulates Heat Shock Factor-1 Expression... in Antioxidants & Redox Signaling, 2007, 9(4): 497-506. After reduction to dihydrolipoic acid, alpha lipoic acid inhibits the activation of NF-kB due to ROS, thus also inhibiting a cascade of cytotoxic and neurotoxic factors. Alpha lipoic acid also protects pancreatic cells placed in contact with inflammatory agents. Furthermore, alpha lipoic acid is useful in the prevention and cure of cataracts [Index]. See the US Patent by Claudio Cavazza (2002), Antioxidant Composition Comprising Acetyl L-Carnitine and Alpha-Lipoic Acid.
Bodybuilding applications of alpha lipoic acid have been explained in Muscle & Fitness Magazine, which claims that alpha lipoic acid improves muscle glucose uptake, improves creatine uptake, and probably boosts endurance performance. However, alpha lipoic acid is used in products for improving muscular definition since it is thought to reduce insulin released when carbohydrates are consumed, increases fat-burning and decreases hunger. 300-600 mg/day is recommended in divided doses. 500-600 mg/dose with 3-5 grams of creatine is taken postworkout to increase creatine uptake. - (dosage after Muscle and Fitness Magazine, 2010). Alpha Lipoic acid activates AMPK, making ATP energy available for life-extending metabolic processes by catabolic action, causing definition improvements, improving autophagy in senescent cells, and energizing pro-inflammatory senescent cell removal by apoptosis.
Alpha Lipoic Acid upregulates HSP expression
Note that alpha lipoic acid increases heat shock protein expression, including the expression of HSP90, which transports transcription factors and transcription factor complex components such as testosterone into the cellular nucleus. HSP90 is also a protein folding chaparone for hTERT, and apparently accelerates hTERT transcription, so that HSP90 may be regarded as a telomerase activator [List]. Note that HSP90 and p23 are required to support telomerase activity.
References
[1] Michael Anderson (2011),
Lipoic Acid Reverses Mitochondrial Decay, Life Extension Magazine, August 2011.
Alpha Tocopherol (pron: Alpha Tow-Cougher-All) [Links, Images, Video, Papers, Patents, Books, LifeExtension] and and Gamma Tocopherol [Links, Images, Video, Papers, Patents, Books, Index, LifeExtension]. Alpha tocopherol and gamma tocopherol are the two most prominent forms of vitamin E in the blood, with alpha tocopherol being 4x as prevalent. Gamma tocopherol is required to quench peroxynitrite radicals, but can be blocked by excess alpha tocopherol. See Index/Vitamin E.
Alteon - Corporate/Alteon, ALT-711 [Links/ALT-711, Images/ALT-711, Video Books, LifeExtension], A.G.E.S, cross-linking fixes, (5).
ALT-711 [MoreLife/ALT-711, Links, Images, Video, Papers, Patents, Books] Alteon, A.G.E.S, cross-linking fixes, (5).
ALT Mechanism [Links, Images, Video, Papers, Patents, Books]. The ALT mechanism for telomere lengthening is exhibited in certain rare cancers. Most cancers (85%-90%) do not use the ALT mechanism. Those that do especially include specific subtypes of soft tissue sarcomas where ALT occurs most often in tumors with complex karyotypes, astrocytic brain tumors and osteosarcomas. The ALT mechanism is believed to be typically due to the failure of an inhibitor (RAP1) in the telomere nucleoprotein complex (Shelterin) to suppress Homologous DNA Repair (HDR), so that telomeric circles (eccDNA) are generated that can perform DNA rolling nanocircle enlongation of telomeres. See (Titia de Lange, 2005).
Aluminium poisoning [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Aluminum poisoning causes neurofibrillary tangles. See aluminum chelation, [13s]. Curcumin chelates aluminum.
Alzheimers Disease, [Wiki/Alzheimers Biochemistry, Ben Best, Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon; prevention, treatment, causes; Brain Deterioration, Dementia, Cognitive Decline, Amyloid Beta, Amyloid Inhibitors, RAGE receptors, Retinoic Acid in Regenerative Medicine, [72], [46s]].
Press for the Rotterdam Study Dementia Charts, Amyloid beta, amyloid beta deposition, and TNF-α [Index] have all been implicated in Alzheimers Disease [Images/Alzheimers Disease Brains], which is treated by supplying both amyloid beta inhibitors [Index, Links, Images, Video, Papers, Patents, LifeExtension] like nattokinase [amyloidosis inhibitor], resveratrol [Index] or acetyl L-carnitine [Index] and TNF-alpha inhibitors [Links, Images, Video, Papers, Patents, LifeExtension] like curcumin, luteolin (found in parsley, sage, peppermint, basil, celery, artichoke, green pepper, perilla and camomile tea) or Enbrel. Anti-inflammatory ginger extract repairs and protects against Alzheimer's Disease-induced behavioral dysfunction [Gao-feng Zeng, Zhi-yong Zhang, Li Lu, De-qiang Xiao, Shao-hui Zong, and Jian-ming He (2013)]. Carnosine [Index] (fighting glycation and chelating copper and iron) and curcumin [Index] are also useful in treating Alzheimers Disease via metal ion chelation, as curcumin chelates aluminum, which produces neurofibrillary tangles. Compounds in cinnamon reduce the aggregation of tau protein that occurs, along with amyloid-beta aggregation, in Alzheimer’s disease (Donald J. Graves, et al, Journal of Alzheimer's Disease, 2013 Jun;36(1)21-40). Cinnamon extract can "inhibit tau aggregation and dissociate tangles in brain tissue derived from Alzheimer’s disease patients" (Life Extension Magazine News, Sept. 2013). Green tea helps prevent Alzheimer's. See Michael Downey (2014), How Green Tea Protects Against Alzheimer’s Disease, Life Extension Magazine, August 2014. Evidently Alzheimers may be triggered by many forms of inflammation that may lead to an amyloid-beta cascade in which amyloid beta triggers TNF-alpha inflammation, leading to further amyloid beta plaques [Images] further increasing TNF-alpha in a destructive chain sequence. Thus amyloid beta can trigger neuronal apoptosis, ravaging and restructuring brains. Amyloid beta is cleared twice as rapidly from the brain during sleep, so loss of sleep can promote Alzheimer's [Mendelsohn and Larrick (2013)]. Sources of inflammation may include a blow to the head, periodontal disease inflammation, or sugar carbonylation of proteins leading to advanced glycation end product accumulation and free-radical inflammation, as in excess consumption of jelly beans leading to Alzheimers Disease. Dark chocolate (Chocolate) is better as candy for old people because it improves circulation in the brain, although cocoa powder includes less fat. Note that microglial cells clean up amyloid beta, but finally fail due to replicative senescence treatable with telomerase activators. By age 90 half of the survivors suffer from Alzheimers Disease, primarily because of the replicative senescence of microglial cells [Images]. "Those getting the most niacin from foods (22 mg per day) were 70% less likely to have developed Alzheimers Disease than those consuming the least (about 13 mg daily), and their rate of age-related cognitive decline was significantly less." Vitamin E suppresses microglial activation caused by amyloids that leads to the production of TNF-alpha and Interleukin 6, so that Vitamin E is neuroprotective and an element in defense against Alzheimers Disease. Patients getting one meal of fish (containing DHA) per week were 60% less likely to get Alzheimers Disease than patients who ate no fish in Chicago and Rotterdam studies. See Russell L. Blaylock, MD (2008), DHA Supports Brain Development and Protects Neurological Function, Life Extension Magazine, Jan 2008. Note that flax seed oil, which contains alpha-linolenic acid, is partially converted in the body to DHA. Alzheimers Disease victims have dramatically lower DHA in the brain hippocampus, the part of the brain managing memory storage, and DHA has been shown to improve age-related memory loss in general. DHA improves memory in both old and young experimental animals. DHA makes up 30% of the brain, and 50% of the retina (op cit). See also Crawford JG (1996), Alzheimers disease risk factors as related to cerebral blood flow, Med Hypotheses, 1996 April;46(4):367-77. "Sugar consumption is identified as a potential risk factor with glucose management in Alzheimers disease also shown to involve reduced cerebral blood flow." Note that exercise [List] improves cerebral blood flow. Saturated fat from animal products increases the risk of Alzheimers Disease. Magnesium deficiency in the brain is associated with synapse loss that is seen in the frontal lobes of Alzheimers patients. Highly absorbable magnesium L-threonate [Images] at 2000 mg/day from The Life Extension Foundation is the most effective magnesium supplement for improving memory scores and rescuing synapses in treating this problem. See also Ott A, Breteler MM, van Harskamp F, et al. (1995), Prevalence of Alzheimers disease and vascular dementia: association with education. The Rotterdam study., BMJ 1995 April 15; 310(6985):970-3 (Dementia Charts). See also Ray B, Lahiri DK (2009), Neuroinflammation in Alzheimers disease: different molecular targets and potential therapeutic agents including curcumin, Curr Opin Pharmacol 2009 Aug;9(4):434-44. Coleman P, Federoff H, Kurlan R (2004), A focus on the synapse for neuroprotection in Alzheimer disease and other dementias, Neurology 2004 Oct 12;63(7):1155-62. Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratidlioni L (2001), Vitamin B(12) and folate in relation to the development of Alzheimers disease, Neurology 2001 May 8;56(9):1188-94. "Abnormal apoptosis of neurons is thought to underlie neurodegenerative disorders such as Alzheimer's and Parkinson's diseases and stroke. Studies of cultured neurons have shown that TERT overexpression can prevent apoptosis in experiments relevant to the pathogenesis of Alzheimer's disease and stroke." - Mark P. Mattson, Peisu Zhang, and Weiming Fu (2000-2012), Roles for TERT and Telomerase in Cell Differentiation and Apoptosis, Marie Curie Bioscience Database. I suspect that exercise regenerates the brain and is required to cure Alzheimer's Disease, an obscure fact that does not sell well to patients who refuse to exercise and would prefer to wolf down any number of pills. Recent research suggests high homocysteine levels lead to Alzheimers [Papers, Patents, Books]. See LuYa-Qin, LuoYu, HeZhong-Fang, ChenJun, YanBo-ling, WangYing, and YuQin (2013), Hydroxysafflor Yellow A Ameliorates Homocysteine-Induced Alzheimer-Like Pathologic Dysfunction and Memory/Synaptic Disorder, Rejuvenation Research, December 2013. See Hydroxysafflor Yellow A [Papers, Patents, Books]. Feeding retinoic acid to lab rats prevents Alzheimer's Disease. See Malcolm Maden's SENS Video Lecture on retinoic acid, regeneration, and applications to neurodegenerative disease.
American Academy of Anti-Aging Medicine - Site/American Academy of Anti-Aging Medicine , [Links, Video] [11].
American Aging Association - Site/American Aging Association newsletter [Links, Video]. See Journals.
Aminoquanidine [IAAS/Aminoquanidine, Links, Images, Papers, Patents, Books, LifeExtension; Links/side effects]. Aminoquanidine is a cross-linking inhibitor [Links, Images, Video, Papers, Patents, Books]. The cross-linking inhibitor aminoquanidine efficiently scavenges methylglyoxal [Images, Papers, Patents, Books], (5). See methyglyoxal scavengers [Images, Papers, Patents, Books].
AMPK (Encyclopedia)
__AMPK-activating Nutraceuticals.
__Telomerase activators also activating AMPK.
Amla, Indian Gooseberry (Phyllanthus emblica) [Wikipedia, Links, Images, Video, Papers, Patents, Books]. Amla is good for endothelial defense, reducing atherosclerotic risk factors and reversing blood vessel changes. It is an anticoagulant. See Life Extension's Vascular Protect. Also see Micheala Harrod (2014), Enhance Endothelial Function and Reduce Arterial Stiffness, Life Extension Magazine March 2014.
Amyloid Beta [Links, Images, Video, Papers, Patents, Books, Life Extension, Amazon, LibCong; RAGE receptors, Alzheimers Disease]. Note that Curcumin attenuates amyloid deposits before or after amyloid deposit formation. Amyloid Beta is cleared out of the brain twice as fast during sleep [Mendelsohn and Larrick (2013)]. See Choi YT, Jung CH, Lee SR, et al. (2001), The green tea polyphenol (-)-epigallocatchin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons, Life Sciences 2001 Dec 21;70(5):603-14. See Index/Green Tea and Index/EGCG. See also Deshpande A, Mina E, Glabe C, Busciglio J (2006), Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons, Journal of Neuroscience 2006 May 31;26(22):6011-8. Lovell MA, Xie C, Xiong S, Markesbery WR. (2003), Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid, J Alzheimers Dis 2003 Jun;5(3):229-39. Patients who have higher levels of the low-density lipoprotein (LDL) cholesterol and lower levels of high-density lipoprotein (HDL) cholesterol have higher levels of amyloid in the brain. - After Bruce Reed; Sylvia Villeneuve; Wendy Mack; Charles DeCarli; Helena C. Chui; William Jagust (2013), Associations Between Serum Cholesterol Levels and Cerebral Amyloidosis, JAMA Neurology, 30 Dec. 2013. "Elevated cerebral [beta-amyloid] level was associated with cholesterol fractions in a pattern analogous to that found in coronary artery disease”. Vitamin B5 (Pantethine) lowers LDL cholesterol levels and reduces the ratio of LDL to HDL cholesterol.
Amyloid Inhibitors [Links, Images, Video, Papers, Patents, Books, LibCong, Life Extension, Amazon]. Amyloid inhibitors include:
(1) Acetyl-L-carnitine [Index, Images, Papers, Patents, Books, LifeExtension, Ref],
(2) Caffeine [Index, Images, Papers, Patents, Books, LifeExtension],
(3) Curcumin [Index, Images, Papers, Patents, Books, LifeExtension],
(4) Pycnogenol [Index, Images, Papers, Patents, Books, LifeExtension].
(5) Resveratrol [Index, Images, Papers, Patents, Books, LifeExtension].
(6) L-3-n-butylphthalide from celery [Images, Papers, Patents, Books, LifeExtension].
(7) CoQ10 [Images, Papers, Patents, Books, LifeExtension].
(8) CoQ10 with Vitamin E [Images, Papers, Patents, Books, LifeExtension].
(9) Alpha Lipoic Acid [Index, Images, Papers, Patents, Books, LifeExtension].
(10) Bacopa [Index, Images, Papers, Patents, Books, LifeExtension].
(11) EGCG [Index, Images, Papers, Patents, Books, LifeExtension].
(12) Nattokinase [Index, Images, Papers, Patents, Books, LifeExtension].
(13) Oleocanthol from Olive Oil (Ref) [Papers, Patents, Books, LifeExtension].

See Peng QL, Buz’Zard AR, Lau BHS (2002), Pycnogenol protects neurons from amyloid-beta peptide-induced apoptosis, Molecular Brain Research 2002, 104(1-2):55-65. The caffeine [Index] in 5 cups of coffee decreases levels of beta-secretase and gamma-secretase, proteins used in amyloid-beta production. See Michael Downey (2012), Discovering Coffee's Unique Health Benefits, Life Extension Magazine Jan 2012.
Amyloid beta inhibitors help prevent Alzheimers Disease. Curcumin attenuates amyloid deposits before or after amyloid deposit formation and chelates aluminum, which can cause neural tangles, as well as other metal ions. Microglial cells [Index] clean up amyloid beta (Aβ), but finally fail due to replicative senescence preventable with telomerase activators. I note that senescent cells gradually aquire more p16INK4a, so that replicative senescence itself is more difficult to reverse as p16INK4A accumulates [Papers]. See the accumulation of p16INK4A [Images, Papers, Patents, Books]. Exercise, resveratrol (via SIRT1), Id-1 helix-loop-helix transcription factor from nerve growth factor (via acetyl L-carnitine, ect), and the telomerase inhibitor retinoic acid from retinol in carrots all inhibit P16INK4A expression, and P16INK4A is a ubiquitinated protein that eventually vanishes if it is not expressed.
Amyloid Inhibitors for other kinds of Amyloid Fibrils and their varieties of Amyloidosis
Note that amyloid fibrils may be based on a variety of precursor proteins that can cause amyloidosis, leading to a corresponding variety of cures and treatments. For instance, genistein may be used to treat or prevent senile systemic amyloidosis, and familial forms of amyloidosis from amyloid fibrils formed from transthyretin protein. Genistein is "an excellent transthyretin amyloidogenesis inhibitor". Nattokinase is able to prevent and dissolve a broad spectrum of amyloidosis amyloid fibrils, including transthyretin amyloid fibrils, amyloid beta amyloid fibrils, prion amyloid fibrils, insulin amyloid fibrils, and beta-microglobulin fibrils.
Amyloidosis (Encyclopedia).
Amyotrophic Lateral Sclerosis (ALS) [Links, Images, Papers, Patents, Books, LifeExtension]. Amylotrophic Lateral Sclerosis (ALS) is a progressive, fatal neurological disease. Risk of ALS can be lowered by supplementing with vitamin E. See LEF News, June 2011. See Index/Brain Degeneration, Index/Dementia, Index/Cognitive Decline, Index/Neurodegenerative Disorders.

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